Medicinal Chemistry Core The Medicinal Chemistry Core provides an integrated approach not only for the synthesis of small molecules, but the assessment of their likely success as translational agents through feedback mechanisms involving biological testing and cheminformatics analyses. The Core anticipates time commitments of 25% for Project 1, 25% for Project 2, and 50% for Project 3. Projects 1 and 2 will initially test aminoglycosides and deoxyglucose analogs, respectively, available through collaborations with other research groups. The Core will provide synthetic services related to these compounds as needed. Project 3 requires the development of glycogen synthase inhibitors through a collaborative process of screening, structure analysis, synthesis and testing. The Core will perform the following Specific Aims: [1] analyze and prioritize structures from high-throughput screening; [2] synthesize glycogen synthase inhibitors for structure-activity relationship generation; and [3] evaluate lead inhibitors in hERG activation, blood-brain barrier permeation, and P-glycoprotein interaction assays.